The work proposed is a continuation of studies of the factors regulating methionine metabolism in mammalian tissues. To this end, we will study the kinetic properties of the individual enzymes catalyzing the reactions leading from methionine to homocysteine; the remethylation of homocysteine; and the conversion of homocysteine to cystathionine. Additional studies will define factors affecting the tissue content of the enzymes. These in vitro studies will be correlated with measurements of methionine metabolism in intact systems (isolated perfused liver, isolated hepatocytes and/or liver slices). BIBLIOGRAPHIC REFERENCES: Freeman, J.M., Finkelstein, J.D., and Mudd, S.H., Folate responsive homocystinuria and "schizophrenia". The N. Engl. J. Med., 292:491, March 6, l975. Finkelstein, J.D., Kyle, W.E., Martin, J.J., and Pick, A.M., Activation of cystathionine synthase by adenosylmethionine and adenosylethionine. Biochem. Biophys. Res. Communs., 66:81-87, l975.